EFFECT OF SELECTIVE COX-2 INHIBITION BY CELECOXIB ON BLOOD PRESSURE AND RENAL FUNCTION IN RATS
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Cyclooxygertase-2 selective inhibitor,represent a new class of nonsteroldal that exhibit preference for inhibition of cyclooxygenase- 2 (COX-2), the COX isoforrn thought to account largely for prostaglandin(PG) formation in inflammation. COX-2 inhibitors have effective antanflammatory action with reduced gastrointestinal toxicity relative to classical NSAIDs which are widely used. Classical NSAIDs are associated with adverse renal effects caused by reduction of renal PG through inhibition of COX. Both isoforms of COX COX-1 & COX-2 are represented in the kidney in constitutive and inducible forms.lt is assumed therefore that the COX-2 inhibitors like celecoxib would have an effect on renal function similar to that of classical NSAIDs. Also,it has been hypothesized that COX-2 inhibitors may increase risk of cardio-vascular events because of their inhibition of vascular prostacyclirt synthesis and lack of an effect on platelet thromboxarte A2 production. The present study was designed to study the effect of chronic administration of COX-2 inhibitor, celecoxib, on blood pressure (BP) and renal A function in normal rats in comparison with non-selective COX inhibitor, indomethacin. Thus, changes in mean arterial blood pressure (MAP) during treatment with celecoxib or indomethrtcin were detected, Also, changes in renal blood flow (RBI) and serum Na, K. urea & creatinirte concentration were all detected after 5 weeks treatment of rats with celecoxib or indomethacirt. Moreover, as chronic treatment with nitric oxide synthetase inhibitor (L-NAME) would cause increased dependance on vascular actions. of prostacyclin. So, in this study, a model of L-NAME induced hypertension in rats was performed and the effect of celecoxib on BP of L-NAME hypertensive rats was detected. Results from this study showed that five weeks treatment of rats with celecoxib in a dose of 10 mg/ kg/day oral caused a significant increase in MAP which started at end of second week and progressively increased till end of fifth week and hypertensive effect of celecoxib was more than that of indomethacin. Both celecoxib and indomethacin caused significant elevation in serum K, urea and creatinine but have no significant effect on serum Na. Indomethacin but not celecoxib caused significant decrease in RBF. In L-NAME hypertensive rats, chronic treatment of such rats with celecoxib in a dose of 10 mg/kg oral daily produced significant elevation of BP in hypertensive rats compared to group given vehicle. These results suggest that COX-2 inhibitors affect vascular and renal functions causing increase in BP and decline in renal function. Thus, COX-2 inhibitors should be used with caution since they are like traditional NSAIDs can interfere with antituypertensive drugs and can cause renal function impairment.